Washington University School of Medicine in St. Louis has received a $7.8 million grant to determine whether the length of time red blood cells (RBCs) are stored affects organ failure in critically ill children who receive RBC transfusions.

The five-year grant, from the National Heart, Lung and Blood Institute of the National Institutes of Health, will fund a trial involving more than 1,500 critically ill children who require RBC transfusions at St. Louis Children’s Hospital and some 30 other medical centers in the United States and Canada.

The trial will be one of the largest studies ever performed in pediatric critical care. Its findings could have significant implications in how RBCs are allocated for critically ill patients.

“We want to know whether fresh red cells can improve outcomes in critically ill children,” said Philip Spinella, MD, associate professor of pediatrics at the School of Medicine and a principal investigator in the study. “No studies have evaluated whether storing RBCs for more than a week affects clinical outcomes for these children.”

The researchers will compare the risk of new or progressive multiple organ failure in two groups of critically ill children ages 3 days to 16 years randomly assigned to receive RBC transfusions as a course of treatment. One group will receive RBCs stored for a week or less, and the other will receive RBCs stored an estimated average of 21 days. (The average length of time that RBCs are stored before being used is 17 days, but this study will exclude young patients who, for specific reasons, always receive fresh RBCs. Their exclusion from the study raises the average storage time to an estimated 21 days.)

Generally, patients who require RBC transfusions receive cells stored anywhere from three to 42 days. The standard approach to allocating RBCs is to use those stored the longest first.

Typically, fresh RBCs are delivered to hospitals in both urban and less populated areas. But when RBCs at hospitals in less populated areas are not used after about 35 days, they are sent to large, specialized medical centers in urban areas — centers including and similar to St. Louis Children’s — where the cells are more likely to be transfused into patients, explained Spinella, who is also a physician in the pediatric intensive care unit at St. Louis Children’s. Blood banks do this in an effort to reduce waste, he said.

RBCs are stored for up to 42 days in the United States and Canada, based largely on survival and recovery studies of RBCs. However, no clinical studies have been performed to show whether RBCs stored for 42 days are effective at delivering oxygen or are as safe as RBCs stored for shorter durations.

Spinella
“It’s like thinking you have a good car because the body is intact,” Spinella explained. “But if the engine does not work, the car is not very functional. The red cells circulate intact, but we have no idea if, when they’re stored for 42 days or close to that, they actually deliver oxygen the way we think they should.”

Spinella, who is also director of the Blood Research Program in Washington University’s Department of Pediatrics, said there is specific interest in determining older RBCs’ effectiveness in critically ill children. Such patients are at risk of experiencing worse outcomes, including multiple organ failure. The researchers want to know whether using fresh RBCs might improve outcomes.

If the new trial finds that fresher RBCs reduce such risks, it could lead to significant changes in how blood is stored and allocated to patients, particularly critically ill children.

The collaborative study also is being funded by the Canadian Institutes of Health Research, which is covering Canada-based costs. The trial’s other co-investigator is Marisa Tucci, MD, of the University of Montreal and Sainte-Justine Hospital in Montreal.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.